Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation
Abstract
:1. Introduction
2. Experimental Section
2.1. Materials
2.2. Methods
2.2.1. Preformulation Study (Selection of SNEDDS Components)
Study of OLM Solubility in Various Oils, Surfactants and Cosurfactants
Preliminary Screening of Surfactants for Emulsification Efficiency
Preliminary Screening of Cosurfactants for Emulsification Efficiency
Construction of Pseudoternary Phase Diagram
2.2.2. Preparation of OLM Loaded SNEDDS
2.2.3. Characterization and Evaluation of OLM Loaded SNEDDS
Thermodynamic Stability Studies
Robustness to Dilution
Assessment of Efficiency of Self-Emulsification
Self-Emulsification Time
Viscosity Determination
Spectroscopic Characterization of Optical Clarity
Transmission Electron Microscopy (TEM)
Droplet Size Analysis and Polydispersibility Index (PDI) Determination
Zeta Potential Determination
Drug Loading Efficiency
In Vitro Drug Release Studies
Kinetic Treatment for the in Vitro Release of OLM SNEDDS (Release Kinetic Modeling)
2.2.4. Preparation of OLM Loaded S-SNEDDS
2.2.5. Characterization of OLM Loaded S-SNEDDS
Micromeritic Properties of S-SNEDDS
3. Results and Discussion
3.1. Preformulation Study (Selection of SNEDDS Components)
3.1.1. Study of OLM Solubility in Various Oils, Surfactants and Cosurfactants
3.1.2. Preliminary Screening of Surfactants for Emulsification Efficiency
3.1.3. Preliminary Screening of Cosurfactants for Emulsification Efficiency
3.1.4. Construction of Pseudoternary Phase Diagram
3.2. Characterization and Evaluation of OLM Loaded SNEDDS
3.2.1. Thermodynamic Stability Studies
3.2.2. Robustness to Dilution
3.2.3. Assessment of Efficiency of Self-Emulsification (Dispersibility Test)
3.2.4. Self-Emulsification Time
3.2.5. Viscosity Determination
3.2.6. Spectroscopic Characterization of Optical Clarity
3.2.7. Transmission Electron Microscopy (TEM)
3.2.8. Droplet Size Analysis and Polydispersibility Index (PDI) Determination
3.2.9. Zeta Potential Determination
3.2.10. Drug Loading Efficiency
3.2.11. In Vitro Drug Release Studies
3.2.12. Kinetic Treatment for the in Vitro Release of OLM SNEDDS (Release Kinetic Modeling)
3.3. Preparation of OLM Loaded S-SNEDDS
3.4. Characterization of OLM Loaded S-SNEDDS
3.4.1. Micromeritic Properties of S-SNEDDS
3.4.2. Reconstitution Properties of S-SNEDDS
3.4.3. Scanning Electron Microscopy (SEM)
3.4.4. Differential Scanning Calorimetry (DSC)
3.4.5. Fourier Transformed Infrared Spectroscopy (FTIR)
3.4.6. Drug Loading Efficiency
3.4.7. In Vitro Drug Release Studies
3.4.8. Pharmacokinetic Study
4. Conclusions
Author Contributions
Conflicts of Interest
References
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Formula | OLM (mg) | Oil (% w/w) | Smix (% w/w) |
---|---|---|---|
F1 | 20 | 5 | 20 |
F2 | 20 | 5 | 40 |
F3 | 20 | 5 | 60 |
F4 | 20 | 5 | 80 |
F5 | 20 | 8.5 | 60 |
F6 | 20 | 8.5 | 80 |
F7 | 20 | 11.5 | 60 |
F8 | 20 | 11.5 | 80 |
Surfactants | % Transmittance * | No. of Inversions |
---|---|---|
Cremophor RH40 | 99.47 ± 0.12 | 4 |
Cremophor S9 | 14.90 ± 0.66 | 17 |
Tween 20 | 98.17 ± 0.40 | 5 |
Tween 40 | 80.97 ± 1.01 | 11 |
Tween 60 | 74.93 ± 0.35 | 9 |
Tween 80 | 97.60 ± 0.26 | 15 |
Span 20 | 52.67 ± 0.75 | 17 |
Span 80 | 56.57 ± 0.50 | 13 |
Labrasol | 44.87 ± 0.95 | 7 |
Cosurfactants | % Transmittance * | No. of Inversions |
---|---|---|
PEG 200 | 99.33 ± 0.38 | 5 |
PEG 400 | 99.53 ± 0.12 | 4 |
PEG 600 | 94.43 ± 0.15 | 4 |
Transcutol HP | 99.83 ± 0.06 | 3 |
Propylene glycol | 98.80 ± 0.26 | 7 |
Glycerol | 99.20 ± 0.10 | 15 |
Formula | Heat-Cool Cycles | Centrifugation Test | Freeze Thaw Cycles |
---|---|---|---|
F1 | √ | √ | √ |
F2 | √ | √ | √ |
F3 | √ | √ | √ |
F4 | √ | √ | √ |
F5 | √ | √ | √ |
F6 | √ | √ | √ |
F7 | √ | √ | √ |
F8 | √ | √ | √ |
Formula | Distilled Water | 0.1 N HCL | Phosphate Buffer pH 6.8 | ||||||
---|---|---|---|---|---|---|---|---|---|
10 | 100 | 1000 | 10 | 100 | 1000 | 10 | 100 | 1000 | |
F1 | √ | √ | √ | √ | √ | √ | √ | √ | √ |
F2 | √ | √ | √ | √ | √ | √ | √ | √ | √ |
F3 | √ | √ | √ | √ | √ | √ | √ | √ | √ |
F4 | √ | √ | √ | √ | √ | √ | √ | √ | √ |
F5 | √ | √ | √ | √ | √ | √ | √ | √ | √ |
F6 | √ | √ | √ | √ | √ | √ | √ | √ | √ |
F7 | √ | √ | √ | √ | √ | √ | √ | √ | √ |
F8 | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Formula | Observations | Grade |
---|---|---|
F1 | Rapidly forming clear emulsion | A |
F2 | Rapidly forming clear emulsion | A |
F3 | Rapidly forming clear emulsion | A |
F4 | Rapidly forming clear emulsion | A |
F5 | Rapidly forming clear emulsion | A |
F6 | Rapidly forming clear emulsion | A |
F7 | Rapidly forming clear emulsion | A |
F8 | Rapidly forming clear emulsion | A |
Formula | Self-Emulsification Time * (s) | % T * | Particle Size (nm) * | PDI * | Zeta Potential (mV) * | Drug Loading Efficiency * (%) |
---|---|---|---|---|---|---|
F1 | 22.38 ± 0.77 | 99.14 ± 0.11 | 17.57 ± 0.26 | 0.076 ± 0.01 | −4.23 ± 0.18 | 92.37 ± 0.75 |
F2 | 20.86 ± 1.26 | 99.30 ± 0.05 | 15.90 ± 0.32 | 0.057 ± 0.04 | −3.62 ± 0.11 | 93.30 ± 0.86 |
F3 | 14.10 ± 0.75 | 98.15 ± 0.12 | 15.33 ± 0.19 | 0.044 ± 0.06 | −2.63 ± 0.47 | 96.85 ± 1.23 |
F4 | 15.55 ± 0.85 | 98.40 ± 0.27 | 14.91 ± 0.12 | 0.056 ± 0.02 | −4.10 ± 0.21 | 95.22 ± 2.22 |
F5 | 18.50 ± 1.38 | 97.97 ± 0.32 | 19.73 ± 0.15 | 0.058 ± 0.02 | −2.88 ± 0.09 | 94.68 ± 1.91 |
F6 | 17.29 ± 1.31 | 99.60 ± 0.14 | 16.49 ± 0.21 | 0.036 ± 0.05 | −3.34 ± 0.16 | 98.52 ± 1.45 |
F7 | 20.20 ± 1.88 | 99.18 ± 0.10 | 22.97 ± 0.44 | 0.077 ± 0.12 | −5.13 ± 0.61 | 96.32 ± 1.88 |
F8 | 19.28 ± 1.13 | 98.33 ± 0.15 | 20.50 ± 0.39 | 0.241 ± 0.09 | −4.47 ± 0.29 | 99.09 ± 0.56 |
Formula | Correlation Coefficients (r) | ||||
---|---|---|---|---|---|
Zero Order | First Order | Second Order | Higuchi’s Diffusion Model | Hixson-Crowell Model | |
F1 | 0.8341 | 0.9053 | 0.9139 | 0.9574 | 0.8829 |
F2 | 0.7962 | 0.8869 | 0.8931 | 0.9486 | 0.8588 |
F3 | 0.8140 | 0.9126 | 0.7213 | 0.9709 | 0.9027 |
F4 | 0.7897 | 0.8632 | 0.8887 | 0.9823 | 0.8424 |
F5 | 0.8181 | 0.9036 | 0.7309 | 0.9758 | 0.9743 |
F6 | 0.9017 | 0.9655 | 0.9862 | 0.9874 | 0.9660 |
F7 | 0.8819 | 0.9501 | 0.7367 | 0.9804 | 0.9640 |
F8 | 0.9016 | 0.9701 | 0.9651 | 0.9963 | 0.9512 |
Formula | In Vitro Drug Release (1 h) | Drug Loading Efficiency | Particle Size | Total Rank Order | Conclusive Rank Order |
---|---|---|---|---|---|
F1 | 8 | 8 | 5 | 21 | 8 |
F2 | 5 | 7 | 3 | 15 | 6 |
F3 | 4 | 3 | 2 | 9 | 1 |
F4 | 3 | 5 | 1 | 9 | 1 |
F5 | 2 | 6 | 6 | 14 | 5 |
F6 | 6 | 2 | 4 | 12 | 3 |
F7 | 1 | 4 | 8 | 13 | 4 |
F8 | 7 | 1 | 7 | 15 | 6 |
Formula | F3 | F4 |
---|---|---|
Angle of Repose | 27.64° ± 1.03° | 22.79° ± 2.22° |
Bulk Density (g/mL) | 0.49 ± 0.02 | 0.51 ± 0.03 |
Tapped Density (g/mL) | 0.59 ± 0.02 | 0.54 ± 0.01 |
Carr’s index (%) | 14.32 ± 1.72 | 12.41 ± 0.95 |
Hausner’s ratio | 1.22 ± 0.10 | 1.08 ± 0.08 |
PK Parameters | S-SNEDDS (F3) | Marketed Product | Drug Suspension |
---|---|---|---|
Cmax (µg/mL) | 26.4320 ± 1.89 | 15.3365 ± 2.18 | 9.5562 ± 2.37 |
tmax (h) | 4 | 3 | 8 |
AUC0–24h (µg·h/mL) | 299.7304 ± 4.15 | 208.3887 ± 6.47 | 143.2684 ± 3.59 |
t1/2 (h) | 7.2489 ± 1.87 | 6.2488 ± 0.94 | 6.0896 ± 1.02 |
Ke (h−1) | 0.0956 ± 0.002 | 0.1109 ± 0.004 | 0.1138 ± 0.001 |
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Nasr, A.; Gardouh, A.; Ghorab, M. Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation. Pharmaceutics 2016, 8, 20. https://doi.org/10.3390/pharmaceutics8030020
Nasr A, Gardouh A, Ghorab M. Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation. Pharmaceutics. 2016; 8(3):20. https://doi.org/10.3390/pharmaceutics8030020
Chicago/Turabian StyleNasr, Ali, Ahmed Gardouh, and Mamdouh Ghorab. 2016. "Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation" Pharmaceutics 8, no. 3: 20. https://doi.org/10.3390/pharmaceutics8030020
APA StyleNasr, A., Gardouh, A., & Ghorab, M. (2016). Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation. Pharmaceutics, 8(3), 20. https://doi.org/10.3390/pharmaceutics8030020